A novel HLA-B*39 allele (HLA-B*3916) due to a rare mutation causing cryptic splice site activation

A novel HLA-B*39 variant, found in an African patient with sickle cell anemia undergoing bone marrow transplantation is described. Initially suspected by inconsistent serological typing (B-blank, Bw6), then recognized by PCR-SSP, and finally characterized by nucleotide sequencing, this novel allele is designated HLA-B*3916. It differs from HLA-B*3910 by a point mutation (G to C) at position 17 of exon 3 causing glutamine to histidine change at codon 96 of alpha(2) domain, a conserved position among HLA class I alleles. cDNA sequence analysis further revealed the presence of both normally and abnormally spliced mRNA species in established cell lines. The abnormal species correspond to partial truncation of exon 3 presumably due to the nucleotide change in exon 3, which constitutes a new consensus acceptor splice site within this exon. We postulate that the observed blank is essentially the consequence of qualitative change in a critical region of this novel antigen as abnormal mRNA species are relatively less abundant than normal species. Because the residue 96 of the HLA class I heavy chain is directly involved in interaction with alpha(2)m, another interesting possibility is that an aminoacid change in this position would perturb such interaction and consequently could affect the serological specificity of B*3916, or its expression or both.     

A novel HLA-B*51 allele (B*5116) identified by nucleotide sequencing

We report here an additional HLA-B*51 variant designated HLA-B*5116. Detected by an abnormal serological reactivity pattern, this variant was identified as a B*51 allele by polymerase chain reaction using sequence-specific primers (PCR-SSP) and characterized by nucleotide sequencing. The new variant sequence match closely with the classical HLA-B*5101 excepted two adjacent nucleotide substitutions at positions 216 and 217 of the third exon and the subsequent Leucine to Glutamic acid change at codon 163 of the alpha2 domain (CTG-->GAG). This new variant was not detected in three different ethnic groups (French, Algerian and Lebanese) suggesting a very rare frequency.     

Acute diuretic activity of aqueous Erica multiflora flowers and Cynodon dactylon rhizomes extracts in rats

Aim of the study

The aim of the present study is to evaluate the diuretic potential and effect on urinary electrolytes of aqueous Erica multiflora L. (Ericaceae) flowers and Cynodon dactylon L. (Poaceae) rhizomes extracts in rats.

Materials and methods

Different concentrations of these plants extract (0.125, 0.250, and 0.500 g/kg of body weight) or the reference drug furosemide (0.015 g/kg) were administrated orally to hydrated male Wistar rats and their urine output was measured at several interval of time after a single dose administration. Furthermore, a toxicological effect of both plants was undertaken as well.

Results

The results showed that furosemide induced significant diuresis and electrolytes excretion during the first hours. Plant extracts increased significantly urinary output and electrolytes excretion at the dose of 0.250 g/kg for Erica multiflora and 0.500 g/kg for Cynodon dactylon. This diuretic effect seems to be not related to K⁺ plant content. Urinary pH remained mostly unchanged during the course of the study for both plant extracts. No lethality was observed among animals when using Erica multiflora even at the dose of 10 g/kg while Cynodon dactylon, instead, caused 50% of rat death (LD50) at 4.5 g/kg.

Conclusion

We concluded that both aqueous herb extracts administered, particularly, at the dose of 0.500 g/kg induce significant effect on urinary output of water and electrolytes and justify their use as diuretic remedy in traditional medicine.     

A novel HLA-B null allele (B*4022N) generated by a nonsense codon in the alpha1 domain

We describe in this work a novel HLA-B null allele designated B*4022N. This new variant was found in a Caucasian individual who was serologically typed for one HLA-B allele as a B-blank, Bw-blank. Retrospective DNA typing by polymerase chain reaction using sequence-specific primers (PCR-SSP) has established the correspondence of this blank allele with the classical HLA-B*4001 allele. Nucleotide sequence analysis of exon 2 and 3 has revealed the presence of two adjacent point mutations at position 170 and 171 of exon 2 (GG to TT). While the first difference is silent, the second leads to the creation of a nonsense codon at position 58 of the alpha1 domain, providing the most likely mechanism underlying the observed null phenotype.     

<Emphasis Type="Italic">Cynodon dactylon</Emphasis> extract as a preventive and curative agent in experimentally induced nephrolithiasis

Cynodon dactylon (Poaceae family) decoction was used in the treatment of kidney stones. However, no scientific study was undertaken so far to demonstrate the beneficial effect of the plant. Thus, the aim of the current study is to evaluate the effect of Cynodon aqueous extract as a preventive and curative agent in experimentally induced nephrolithiasis in a rat model. Ethylene glycol (EG) was used in the experiment to induce calcium oxalate (CaOx) deposition into kidneys. In preventive protocol, Cynodon decoction was administered in the same day with EG to evaluate the ability of the extract to prevent crystal deposition. However, in curative protocol, rats were first rendered nephrolithiasic and then the extract was administered to assess the ability of the plant to eliminate the pre-existing crystal deposition. In both protocols, urinary biochemical and other variables were measured during the course of the study. Crystalluria and renal histology were examined as well. The results showed that, in both protocols, all measured variables were similar for both the rat groups. Nevertheless, urinary biochemical analysis was apparently unaffected by the extract except oxalate in preventive protocol, and calcium, sodium, and potassium in curative protocol which were significantly highly excreted in treated rats compared to untreated animals. Crystalluria was characterized mostly by the presence of large quantities of CaOx monohydrate and CaOx dihydrate particles in untreated rats. However, crystalluria was mainly dominated by the presence of CaOx dihydrate particles with reduced size. The most apparent beneficial effect of Cynodon extract was seen in kidney tissues where reduced levels of CaOx deposition have been noticed especially in medullary and papillary sections from treated rats. We concluded that C. dactylon extract has beneficial effect in preventing and eliminating CaOx deposition into kidneys. Such findings provide a scientific explanation for its use in the treatment of kidneys stones.     

Traitement par olmésartan et entéropathie : à propos de deux cas et revue de la littérature

Introduction

Olmesartan is an angiotensin II receptor blocker, used to treat arterial hypertension. Severe digestive manifestations have been associated with olmesartan, including sprue-like enteropathy and lymphocytic colitis.

Bioscreening and pre-clinical evaluation of the impact of bioactive molecules from Ptychotis verticillata on the multilineage potential of mesenchymal stromal cells towards immune- and inflammation-mediated diseases

Objective and design

Mesenchymal stromal cells (MSCs) are currently used in cell reparative medicine due to their trophic and ant-inflammatory properties. The modulation of stem cell properties by phytochemicals has been suggested as a tool to empower their tissue repair capacity. In vitro, MSCs are characterized by their tri-lineage potential that holds great interest for tissue regeneration. Ptychotis Verticillata (PV), an aromatic and medicinal plant, may be thus used to modulate the in vitro multilineage potential of MSCs.

Materials and methods

We screened the impact of PV-derived essential oil and their bioactive molecules (thymol and carvacrol) on the in vitro multilineage potential of MSCs. Different concentrations and incubation times of these compounds were assessed during the osteogenesis and adipogenesis of MSCs.

Results

The analysis of 75 conditions indicates that these compounds are biologically active by promoting two major differentiation lineages from MSCs. In a time- and dose-dependent manner, thymol and carvacrol increased the osteogenesis and adipogenesis.

Conclusion

According to these preliminary observations, the addition of PV extract may stimulate the tissue regenerative and repair functions of MSCs. Further optimization of compound extraction and characterization from PV as well as cell treatment conditions should increase their therapeutic value in combination with MSCs.

     

Association of PTPN22 gene functional variants with development of pulmonary tuberculosis in Moroccan population

Mycobacterium tuberculosis , the causal agent of pulmonary tuberculosis (TB), remains a major health problem throughout the world causing high mortality in humans. Previous studies showed that several genes may play crucial roles in susceptibility to TB. The PTPN22 gene encodes the lymphoid tyrosine phosphatase that has an important regulatory effect on T- and B-cell activation in immune response. The purpose of this study was to investigate the role of two functional missense single nucleotide polymorphisms (SNPs) of the PTPN22 gene region (R620W and R263Q) in the susceptibility to TB in the Moroccan population. A case–control association study was performed including 123 pulmonary TB patients and 155 healthy controls. All subjects were genotyped by TaqMan SNP genotyping assays. Regarding the PTPN22 R620W (C1858T) SNP, we observed a statistically significant difference in the distribution of the PTPN22 1885T allele between pulmonary TB patients and healthy controls (0.41% vs 3.2%, P  = 0.01, odds ratio (OR) = 0.14, 95% confidence interval (CI) = 0.01–0.93). With respect to the PTPN22 R263Q (G788A), we observed an increase of 788A allele frequencies in TB patients compared with those in healthy controls (3.65% vs 0.65%, P  = 0.01, OR = 5.85, 95% CI = 1.17–39.55). These results suggest that PTPN22 gene variants may affect susceptibility to TB in the Moroccan population.